The completeness of the surgical resection is an important factor for the prognosis of brain tumor patients. In trying to achieve more complete glioma resections, the surgeon encounters several hurdles, which include irregular and indistinct tumor margins as well as tumor growth adjacent to or invading crucial neurological structures. A wide variety of techniques have been explored to date in an effort to better visualize tumor margins. For instance, pre-operative magnetic resonance imaging (MRI) has been used to guide stereotactic surgery, where the MR images are used to determine the macroscopic outline of the tumor. However, these methods suffer from limited spatial resolution and incongruencies between pre-operative MRI and actual tumor borders during surgery due to brain shift. Intra-operative MRI usually requires the administration of gadolinium (Gd)-chelates, which suffer from short blood half-life requiring repeated injections, high dosages and inaccuracies due to surgically induced false-positive contrast enhancement. Several intra-operative optical methods have been suggested, either based on intrinsic tissue optical properties or exogenous contrast agents. However, these optical techniques suffer from poor specificity due to tissue autofluorescence, limited resolution and depth of penetration, which ultimately limit localization of the true brain tumor margins.